Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni:: IFN-γ is associated with protection against fibrosis and TNF-α with aggravation of disease
Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni:: IFN-γ is associated with protection against fibrosis and TNF-α with aggravation of disease
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DOI：
10.4049/jimmunol.169.2.929
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发表时间：
2002-07-15
影响因子：
4.4
通讯作者：
Dessein, AJ
中科院分区：
文献类型：
--
作者：
Henri, S;Chevillard, C;Dessein, AJ
肝门静脉周围纤维化，影响5 - 10%的曼氏血吸虫感染的受试者，是由T细胞依赖性肉芽肿引起的，这些肉芽肿在曼氏血吸虫卵周围发展。感染的实验模型已经表明肉芽肿和纤维化受到细胞因子的严格调节。然而，目前尚不清楚为什么晚期门静脉周围纤维化仅发生在某些受试者中。本研究的目的是评估S.曼氏感染的晚期肝病患者，试图将门静脉周围纤维化的易感性与调节肉芽肿和纤维化的细胞因子的异常产生联系起来。通过超声对苏丹一个村庄的795名居民进行了纤维化评估，其中S。曼索尼病是地方病：在12%的人群中观察到晚期门静脉周围纤维化; 35%的受影响的受试者表现出门静脉高压的迹象。年龄（比值比（OR），11.5），性别（OR，4.2）和感染水平（OR，2.2）与肝纤维化显著相关（p ≤ 0.01）。测定了99名受试者（75名无或轻度纤维化; 24名晚期纤维化）的卵刺激血液单核细胞产生的细胞因子。细胞因子水平的多变量分析显示，高IFN-γ水平与纤维化风险显著降低相关（p = 0.01; OR，0.1）;相反，高TNF-α水平与门静脉周围纤维化风险增加相关（P = 0.05; OR，4.6）。此外，感染水平与IFN-γ的产生呈负相关。这些结果与实验模型中的观察结果强烈表明，IFN-γ在S.曼氏菌感染的患者对抗门静脉周围纤维化，而TNF-α可能加重疾病。
Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12 % of the population; 35 % of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p less than or equal to 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-gamma levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-alpha levels were associated with an increased risk (P = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-gamma production. These results with observations in experimental models strongly suggest that IFN-gamma plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-alpha may aggravate the disease.